Advantages of 1-1-12 Wash in Scheme during Induction with Low Flow Anesthesia with and without Nitrous Oxide.

INTRODUCTION: In the past, many wash-in schemes have been used with initially high fresh gas flow (FGF) to achieve the necessary alveolar concentration of inhalational agent in 10-15 min. This study was designed to show whether 1-1-12 wash-in scheme proposes an earlier achievement of induction or is there any requirement of high FGF phase to know the time taken for induction with and without nitrous oxide (N2O). AIMS: The aim of the study was to find out the time required for the alveolar concentration of desflurane to be from 1% to 6% with and without N2O.
DESIGN: It was a potential randomized study which was conducted on sixty patients admitted for elective surgery.
MATERIALS AND METHODS: Two groups of thirty patients each were made and randomly assigned. Group N received desflurane with N2O plus oxygen and Group A received desflurane with air plus oxygen. STATISTICAL ANALYSIS: The observations were noted and evaluated accordingly. Analysis was done using unpaired t-test.
RESULTS: Hemodynamic parameters were almost similar in both the groups. In Group N, gradual FAD (Alveolar Desflurane concentration, i.e., end-tidal desflurane) from 1% to 6% was achieved at 0.5, 1, 1.5, 2, 3, and 4 min. In Group A, the same was achieved at 0.6, 1, 1.5, 2, 3, and 4 min (P > 0.05). No significant difference was found between the recuperation time and score in both the groups. Rather complications were more in Group N and statistically significant for nausea and vomiting.
CONCLUSION: Time taken to attain FAD from 1% to 6% was 4 min in both the groups. It is concluded that the recitation of 1-1-12 wash-in scheme is autonomous on the use of N2O and high FGF phase.

INTRODUCTION

The beginning of modern inhalational agents such as desflurane and sevoflurane[1] revolutionized the world. The use of low-flow anesthesia (LFA) with these agents offers the advantage of creating less pollution, better body dynamics, and it is also less expensive.[23] Nitrous oxide (N2O), an inorganic inhalation agent, is in use for the past 150 years for its analgesic and anxiolytic properties,[4] but in recent years, certain disadvantages associated with it have come into notice. These include a high incidence of postoperative nausea and vomiting, pink gas effect/diffusion hypoxia and potential for hypoxic gas mixture, workplace pollution, greenhouse effect, and teratogenicity.[5] Keeping all these limitations in view, it is desirable to omit N2O in long-duration surgeries. Previously used wash in schemes using LFA necessitated initial high flow and required 10–15 min to attain minimum alveolar concentration (MAC) value of one. In our study, we used the 1-1-12 principle and found out the time required for the rise of alveolar desflurane concentration from 1% to 6% (FAD) and the revival characteristics with or without N2O. From the side effects or complications point of view, with and without N2O, omission of N2O was a better and feasible option.

Our proposed 1-1-12 wash-in scheme is a fast and simplified wash-in technique that starts with a fresh gas flow (FGF) of N2O:O2 at 1:1 L/min and a vaporizer concentration of desflurane (FD) of 12%. In this wash-in scheme, we start with 1 L flow of N2O/air and 1 L flow of O2 and set the dial vaporizer concentration at 12%. We allow 6% FAD to be achieved, then the FGF of O2:N2O or O2:air is reduced to 0.5:0.5 L/min and the dial concentration is adjusted accordingly to keep MAC value around 1%. Although the dial concentration was initially kept high at 12%, it helped in achieving the required FAD in <5 min. The FD was decreased according to bispectral index (BIS) and MAC values so that measured value of desflurane went to patient and there was no unnecessary wastage of gases and pollution. Our scheme thus aims at an earlier and easier achievement of every gradual FAD from 1% to 6% using LFA in a more competent and safer way without N2O. It helps in achieving the gradual FAD at an earlier time compared to traditional methods and also does not need the initial use of high-flow anesthesia.

MATERIALS AND METHODS

According to the American Society of Anesthesiologists (ASA), patient's physical status ASA Classes I or II, a randomized study on sixty patients was conducted after getting the approval from the Institutional Ethics Committee and the written consent of the patients. The patients were scheduled to undergo surgery under general anesthesia and in the age group of 20–60 years. The following types of patients were excluded from the study such as pregnant woman, morbidly obese, and patients with physical status ASA Classes III or higher and emergency surgeries.

Two groups of thirty patients each were made and randomly allocated depending on the carrier gas and volatile anesthetic agent. Each patient received a randomization number and was put in the group according to his/her number. Group N received LFA using volatile anesthetic desflurane with N2O (O2 50%:N2O 50%), whereas Group A received LFA using volatile anesthetic desflurane with air (O2 50%:air 50%). The routine preanesthetic checkup, investigations, and airway assessment were made 1 day before the surgery. Patients were given alprazolam 0.25 mg and pantoprazole 40 mg a night before surgery and were kept fasting up to 8 h before surgery.

The preoperative reassessment was done on the day of surgery. Multipara monitor was attached. Heart rate was checked by electrocardiography electrodes. Respiratory rate, systolic and diastolic blood pressure (SBP and DBP), mean arterial blood pressure, and SpO2 were also monitored time to time. The level of anesthesia was also monitored by BIS sensor attached to the monitor. Intravenous (IV) drip was initiated with Ringer's lactate at 10 ml/kg according to the 4:2:1 fluid formula. A standard circle circuit with a soda lime absorber was used. Heart rate and blood pressure were documented before induction for a baseline.

IV dexmedetomidine (1 μg/kg) was given to the patients for 10 min in infusion as a premedication before induction. Patients were preoxygenated at the rate of 10 L/min for 3 min with pure oxygen. Anesthesia was persuaded with i.v propofol 2 mg/kg. Endotracheal intubation was made possible with vecuronium using the priming principle. Ventilation was managed using a FGF of O2:N2O at 1:1 L/min in Group N and O2:air at 1:1 L/min in Group A with 12% vaporizer concentration of desflurane (FD). Initial respiratory rate (12 per min) was set up and regulated to keep the PaCO2 around 30–35 mmHg. Time to attain alveolar desflurane concentration (FAD) of 1%–6% was noted. After 6% FAD was realized, the FGF of O2:N2O or O2:air was reduced to 0.5:0.5 L/min, and the FD was adjusted accordingly to keep MAC value around 1% for adequate depth of anesthesia. Hemodynamics were monitored every 5 min interval during surgery till the end.

The inhalational anesthetic vaporizer was switched off 5 min earlier to the end of surgery. N2O was then stopped in Group N, air was stopped in Group A, and only oxygen was passed at the rate of 6 L/min. After 20 min of the last dose of relaxant, neostigmine (0.05 mg/kg) and glycopyrrolate (0.01 mg/kg) were intravenously administered to reverse the neuromuscular block. The trachea was extubated after its criteria such as recommencement of regular respiratory pattern, enough minute ventilation, oxygen saturation >95%, and continuation of airway reflexes were met. The patient was then transferred to the postanesthesia care unit (PACU).

Recovery time is defined as the time of termination of the inhalational of anesthetic agent (vaporizer switch off) to the time of the patient opened his/her eyes on the oral command while recuperating from anesthesia. Patient recovery score was defined before shifting to recovery room (1 = no response to painful stimuli; 2 = drowsy but arousal by oral command; and 3 = awake and reacting to command at extubation). Both the recovery time and score were noted at the end of surgery.

A revival profile was maintained according to the Aldrete Scoring System as follows:

Activity

Able to move 4 extremities on command – 2

Able to move 2 extremities on command – 1

Able to move 0 extremities on command – 0.

Breathing

Able to breathe deeply and cough freely – 2

Dyspnea – 1

Apnea – 0.

Circulation

SBP =20% of preanesthetic level – 2

SBP =20%–49% of preanesthetic level – 1

SBP =50% of preanesthetic level – 0.

Consciousness

Fully awake – 2

Arousable – 1

Not responding – 0.

Pulse oximetry

92% while breathing room air – 2

Needs supplemental oxygen to maintain SpO2 90% – 1

90% even with supplemental oxygen – 0.

If the total score was ≥9 in 24 h, the patient was discharged from PACU.

The parameters recorded are as follows: hemodynamic characteristics (pulse rate, mean arterial blood pressure, SBP, DBP, and oxygen saturation), BIS, mean end-tidal anesthetic agent concentration, MAC, end-tidal carbon dioxide, end-tidal N2O and inspired oxygen concentration, recovery time and score using the Aldrete score, and any critical event.

The data were collected, compiled, and analyzed statistically. Sample size was analyzed keeping in view at most 5% risk with minimum 85% power and 5% significance level. Unpaired t-test was used to analyze. Significance level was evaluated by knowing the P value. The P > 0.05 was considered nonsignificant; P = 0.01–0.05 was considered significant; and P < 0.01 was considered highly significant. The results were examined and compared with literature results (SPSS 22 version of software was used, IBM Corp., 2013, Armonk, NY, USA).

RESULTS

With respect to the demographic parameters, the patients in both the groups were analogous as is evident from Table 1. The duration of surgery in Group N was 46.00 ± 9.43 min and in Group A was 47.00 ± 10.77 min. The difference was statistically nonsignificant (P > 0.05). Hemodynamic parameters were also statistically and clinically insignificant (P > 0.05).

Table 1

Demographic characteristics of patients who received low-flow anesthesia with desflurane as inhalational anesthetic agent

In Group N, the FAD (end-tidal desflurane) concentration rose quickly and linearly from 0% to 4% within 2 min [Table 2]. An FAD of 5% and 6% was accomplished at 3 and 4 min, respectively. In Group A, gradual FAD from lower to higher level (1%–6%) was attained in 4 min (P > 0.05). Thus, in both the Groups N and A, a 6% FAD was obtained within 4 min.

Table 2

Mean end-tidal concentration (Etin) of inhalational anesthetic agent (desflurane)

In both the Groups N and A, a MAC value of 1% was achieved in 4 min (P > 0.05) [Table 3]. Although MAC was greater in Group N, it was statistically nonsignificant, and in both the groups, the dial concentration was changed to maintain MAC around 1%.

Table 3

Mean minimum alveolar concentration of inhalational anesthetic agent (desflurane)

BIS was lower in Group N as compared to Group A during the whole surgery period, showing the deeply anesthetized patients in Group N compared to Group A. The difference was statistically nonsignificant (P > 0.05) although it was clinically significant.

The mean end-tidal N2O concentration in Group N ranged from a minimum value of 20.30 ± 1.32 to a maximum value of 60.03 ± 1.47 during 60 min period. It was observed that N2O concentration rose up to 10 min and then fell over time. The O2 level in Group N varied between 42.73 ± 1.80 and 70.00% ±1.93%, whereas in Group A, it varied between 58.13% ±17.89% and 80.90% ±1.42%. The difference of values between the two groups was statistically significant (P = 0.01–0.05) but not clinically. In both the groups, end-tidal CO2 concentration was retained between 35 and 45 mmHg.

Recovery time in Group N was found to be 5.89 ± 0.13 min, and in Group A, it was 5.78 ± 0.45 min. In Group A, 21 patients were alert and awake and 9 were sleepy but arousable out of 30. In the Group N, 11 patients were sleepy but arousable and 19 patients were alert and awake out of 30. The difference between the two groups was not statistically significant (P > 0.05). The Aldrete score for both Groups N and A was comparable (8.93 and 9.07 min, respectively, P > 0.05) [Table 4].

Table 4

Comparison of recovery time (min) and Aldrete score between Group N and Group A

Comparison of both the groups was made for intraoperative (hypotension and dysrhythmias) and postoperative complications (nausea, vomiting, and laryngospasm). Difference between the two groups was statistically nonsignificant (P > 0.05) for hypotension, dysrhythmias, and laryngospasm but was statistically significant (P = 0.03) for nausea and vomiting. The total number of patients with complications was higher in Group N than in Group A.

DISCUSSION

In circle system, efficient and competent use of LFA technique is dependent on the volatile agent used. Significant savings can be attained with lower flows of N2O and O2, but highest saving occurs with volatile agent such as desflurane.[67] Desflurane having low tissue solubility is well matched for LFA.[8] Initial high FGF with high dial vaporizer concentration of desflurane (FD) is needed for LFA. This is required to attain the required concentration in the circle circuit, called the wash-in phase. Most of the reported wash-in schemes needed higher FGF or vaporizer concentration of desflurane yet realized only some of the alveolar concentration (FAD).[8910]

Agents requiring a long duration of initial high flow usually defeat the purpose of LFA; however, newer agents such as desflurane and sevoflurane, because of low blood gas solubility, require less time to achieve the desired MAC. Thus, the initial duration of high FGF can be reduced which adds on to the advantage of LFA and increases the circle system efficiency.[8]

Our aim was to establish a 1-1-12 wash-in scheme to allow earlier and easier attainment of every FAD from 1% to 6% in a safe and efficient way without using N2O. In both the Groups N and A, FAD of 6% was accomplished within 4 min. Since the time needed in both the groups are equal, it can be wrapped up that the need for carrier gas (N2O) in LFA with desflurane is questionable. Sathitkarnmanee et al. in 2015 proposed a similar scheme.[11] They observed that a gradual increase of FAD from 1% to 7% took place at 0.6, 1, 1.5, 2, 3, 4, and 6 min, respectively.[11] It was extended till the FAD achieved was 7% to get a better depth of anesthesia. Our study accomplished gradual FAD from 1% to 6% at 0.6, 1, 1.5, 2, 3, and 4 min in Group A, and we did not extend the FAD to be achieved to 7% in this Group since the BIS levels in both the groups were comparable as seen from Figure 1.

Figure 1

Mean bispectral index at different time intervals in Group N and Group A

MACs of desflurane in both the groups were measured during surgery. Although MAC was higher in Group N, the dial concentration in both the groups was changed to maintain MAC at 1%. A study published in 2014 by Sathitkarnmanee et al. proposing a scheme for desflurane-N2O-LFA where they reported that every gradual FAD from 1% to 6% was achieved at 0.6, 1, 1.5, 2, 3, and 4 min.[12] Our study of Group N is in conformity with the above study.

BIS was found to be lesser in Group N as compared to Group A during the surgery indicating that the patients in Group N were more intensely anesthetized as compared to Group A. The difference between them was not statistically significant (P > 0.05) indicating the intensity of anesthesia was clinically comparable in both the groups. Patients did not have any history of intraoperative alertness before getting freed from the recovery room. The slight increase in BIS level at 1 min after intubation might be due to the sympathetic response. A dose-dependent decrease in BIS induced by N2O was also reported in literature by Hans et al.[13]

Mean end-tidal N2O concentration was measured in Group N from 1 to 60 min. The initial rise in N2O could be credited to the introduction of N2O into the circle system after intubation. The O2 level at 0 min was 100% in both the groups due to preoxygenation. At 1 min, it was 100% in both the groups since N2O or air was not introduced into the circle system yet. The concentration did not fall below 30% at all. The difference between the two groups was statistically significant (P = 0.01–0.05) but not clinically. Since Group N contained N2O plus oxygen and Group A contained air plus oxygen, thus the end-tidal O2 concentration was higher in Group A. A study was conducted by Garg in 2012 where it was reported that, in LFA, N2O showed a falling trend over time.[14] It was also viewed that O2 is consumed in the body and have a decreasing trend over time [Figure 2]. Similar results were reported by Mallik et al. in 2012.[15]

Figure 2

Mean inspired oxygen concentration at different time intervals in Group N and Group A

Recovery time and score were almost similar in both the groups. Aldrete score was monitored in PACU and the washout time for N2O was 3–5 min. The Aldrete score for both the Groups N and A was comparable, 8.93 and 9.07 min, respectively. The difference between the two groups was statistically nonsignificant (P > 0.05) indicating no change in recovery characteristics when desflurane was given with or without N2O. An article was published in January 1998 by Crawford et al. in which they mentioned that N2O had little effect on the rate of recovery after propofol but significantly increased the occurrence of postoperative emesis.[16] Other studies also showed that the early recovery with desflurane was due to its low blood gas solubility and rapid elimination.[1718]

The number of patients with complications was higher in Group N than in Group A and nausea and vomiting was more (13.33%) in Group N because of N2O use [Figure 3]. N2O is known to create the disturbance in the metabolism of methionine and folate. Between May 30, 2008, and September 28, 2013, an international, randomized, assessor-blinded trial (ENIGMA II) was performed by Myles et al.[19] in 7112 patients (age ~ 45 years) with identified or suspected coronary artery disease undergoing noncardiac surgery. They also reported secondary outcome like undesirable effects such as nausea and vomiting. About 3483 patients receiving N2O and 3509 without N2O were assessed. Severe nausea and vomiting took place in 506 patients (15%) assigned to N2O, while 378 patients (11%) not assigned to N2O (P < 0.0001). Thus, it was interpreted that anesthesia without the use of N2O is more patient-friendly.

Figure 3

Intraoperative and postoperative complications in Group N and Group A

The advantages of our wash-in scheme (1-1-12) were less requirement of FGF (no initial phase of high-flow anesthesia was required), simplicity, flexibility (in terms of using air in place of N2O), coverage (the range of FAD covers concentration for both unbiased and pure inhalation anesthesia), and minimum operating room pollution and safety (medical air is ecologically safe).

MACBAR is a variant of MAC which was first described in 1981.[20] It is defined as the brain concentration of agent-blocking adrenergic responses to skin incision.[21] MACBAR for desflurane is found to be 1.3 MAC.[22] Our scheme resulted in rapid wash-in, passing MACBAR of desflurane earlier and thus keeping the patient in surgical stage of anesthesia earlier.

It may be concluded that the time taken to achieve FAD from 1% to 6% in our study with air is the same as that with N2O (4 min). Our results demonstrated that the performance of 1-1-12 wash-in scheme is not dependent on the use of N2O. N2O did not influence the uptake of desflurane as both N2O and desflurane have almost equally very low blood gas solubility (0.47 and 0.42, respectively). Thus, our scheme required less FGF to achieve FAD from 1% to 6% in 4 min which is more rapid and easier than most of the wash-in schemes used in the past.

Limitations

Although results of our study were conclusive, we feel that larger sample size would have been more beneficial for making future guidelines. We also did not calculate end-tidal air concentration.

CONCLUSION

It is concluded that LFA using 1-1-12 wash-in scheme with desflurane and omitting N2O has an added benefit of rapid attainment of FAD without the initial high-flow phase. It has a comparable depth of anesthesia, comparable recovery profile and score, and minimal intra- and postoperative complications. Thus, circle system in a more safer and efficient way can be used.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.